| Project/Area Number |
23790839
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SAWAKI Daigo 東京大学, 医学部附属病院, 特任助教 (40456132)
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| Research Collaborator |
SUZUKI Toru 東京大学, 大学院・医学系研究科, 特任准教授
AIZAWA Kenichi 東京大学, 大学院・医学系研究科, 特任助教
MATSUMURA Takayoshi 東京大学, 大学院・医学系研究科, 特任助教
ISHIDA Zyunichi 東京大学, 医学部附属病院, 特任助教
孫 輔卿 東京大学, 大学院・医学系研究科, 特任研究員
NAGAI Ryozo 自治医科大学, 学長
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 分子血管病態学 / 転写因子 / 大動脈瘤 / TGFβ / 大動脈 |
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| Research Abstract |
Previous studies suggest that Kruppel-like factors (KLFs) play important roles in the cardiovasculature. Preliminary studies indicated that KLF6 have roles in cardiovascular development and remodeling such as cardiac fibrosis. In this study, we next aimed to decipher the mechanism in which KLF6 mediates aortic pathologies such as aortic aneurysm or dissection. Continuous angiotensin II (AngII) infusion in klf6+/- mice resulted in decreased TGFbeta-1 expression levels both in aortic wall and serum in KLF6+/- mice, and diminished blood pressure increase (wild-type 150-160 mmHg, KLF6+/- 100-120 mmHg), which indicates possibility of blood pressure control gy KLF6 inhibition. On the other hand, KLF6+/ mice showed accelerated aortic remodeling such as inflammatory cell infiltration or MMP-2 induction and aortic walldestruction in aortic aneurysm/dissection formation with AngII + Cacl2. These data collectively showed the biphasic mechanism in aortic pathologies, indicating the importanc of meticulous decision of KLF6 targeting therapies.
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